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Leukemia & Lymphoma Volume 48, 2007 - Issue 10
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Original Article: Research

Mesenchymal stem cell abnormalities in patients with multiple myeloma

Laurent Garderet INSERM, U832, EA1638, Paris, F-75012 France, Université Pierre et Marie Curie-Paris 6, Site de Saint Antoine, 27 rue Chaligny, Paris, F-75012, France; Hematology Department, Saint Antoine Hospital (APHP), 186 rue du Faubourg St Antoine, F-75012, France
,
Christelle Mazurier INSERM, U832, EA1638, Paris, F-75012 France, Université Pierre et Marie Curie-Paris 6, Site de Saint Antoine, 27 rue Chaligny, Paris, F-75012, France
,
Alain Chapel INSERM, U832, EA1638, Paris, F-75012 France, Université Pierre et Marie Curie-Paris 6, Site de Saint Antoine, 27 rue Chaligny, Paris, F-75012, France; IRSN, BP 17, 92262, Fontenay aux Roses Cedex, France
,
Isabelle Ernou Research Department, Jean Julliard Army Blood Transfusion Centre, 1 rue Lieutenant Raoul Batany, BP 410, 92141, Clamart Cedex, France
,
Laetitia Boutin Research Department, Jean Julliard Army Blood Transfusion Centre, 1 rue Lieutenant Raoul Batany, BP 410, 92141, Clamart Cedex, France
,
Xavier Holy Aerospace Physiology Department, Aerospace Medical Institute, Army Health Service, BP 73, 91223, Brétigny sur Orge Cedex, France
,
Norbert Claude Gorin INSERM, U832, EA1638, Paris, F-75012 France, Université Pierre et Marie Curie-Paris 6, Site de Saint Antoine, 27 rue Chaligny, Paris, F-75012, France; Hematology Department, Saint Antoine Hospital (APHP), 186 rue du Faubourg St Antoine, F-75012, France
,
Dr. Manuel Lopez INSERM, U832, EA1638, Paris, F-75012 France, Université Pierre et Marie Curie-Paris 6, Site de Saint Antoine, 27 rue Chaligny, Paris, F-75012, FranceCorrespondence[email protected]
,
Christelle Doucet Research Department, Jean Julliard Army Blood Transfusion Centre, 1 rue Lieutenant Raoul Batany, BP 410, 92141, Clamart Cedex, France
&
Jean-Jacques Lataillade Research Department, Jean Julliard Army Blood Transfusion Centre, 1 rue Lieutenant Raoul Batany, BP 410, 92141, Clamart Cedex, France
 show all
Pages 2032-2041 | Received 09 Jun 2007, Accepted 19 Jul 2007, Published online: 01 Jul 2009
 
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Abstract

Osteolytic bone lesions are common in patients with multiple myeloma (MM), a clonal plasma cell disorder, and result from increased osteoclastic bone resorption and decreased osteoblastic bone formation. Because mesenchymal stem cells (MSCs) are committed towards cells of the osteoblast lineage, we compared the in vitro characteristics of MSCs from the bone marrow of 18 MM patients (MM-MSCs) and eight normal donors (ND-MSCs). MM-MSCs displayed deficient growth that could be explained in part by the reduced expression of several growth factor receptors on the surface of MM-MSCs compared with ND-MSCs. Receptor downregulation was observed on RT-PCR analysis. A major finding was an approximately fivefold higher expression of osteoblast inhibitor DKK1 at transcript and protein levels in MM-MSCs than ND-MSCs. These data suggest that defective osteoblast function in patients with advanced MM may be related not only to factors released by tumor myeloma cells but also to MSC abnormalities.

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